Nomifensine maleate (Merital) is a norepinephrine-dopamine reuptake inhibitor[1] test-marketed in the United States by Hoechst AG (now Novartis) that increases the amount of synaptic dopamine available to receptors by blocking dopamine's re-uptake transporter. This is a mechanism of action shared by drugs of abuse like cocaine (which tend also to cause dopamine release) and antidepressants such as bupropion (Wellbutrin/Zyban).

Merital was investigated for use as an antidepressant in the 1970s, and was found to be a useful antidepressant at doses of 50-225mg per day, both motivating and anxiolytic. There were relatively few adverse effects (mainly dry mouth, headache, nausea), the drug was not sedating, did not interact significantly with alcohol and lacked anticholinergic effects. No withdrawal symptoms were seen after 6 months treatment. The drug was however considered not suitable for agitated patients as it presumably made agitation worse.

Later studies in the 1980s concluded that there was potential for dependence and abuse of nomifensine, typically in patients with a history of stimulant addiction, or when the drug was used in very high doses (400-600mg per day). Nomifensine is now only rarely used as an antidepressant due to concerns about causing haemolytic anaemia, and problems with overstimulation and hyperthermia in overdose. It has been investigated for use in treating ADHD and animal models of Parkinson's disease with some success. However, it has not proved of benefit to human patients suffering from advanced Parkinsonism. [2][3][4]

Nomifensine was withdrawn from mainstream medical use for a variety of reasons, abuse potential being a concern, but also problems with kidney and liver toxicity and haemolytic anaemia were cited, and some deaths were linked to the use of this compound although the mechanism remains unclear. A likely cause of nomifensine toxicity is the aromatic amine group, as compounds containing this chemical substructure are notorious for producing toxic metabolites.[5]

Nomifensine is now mainly used in scientific research, particularly in studies involving dopamine release in response to addiction. This is because typically different areas of the brain have different amounts of dopamine transporter, but when Nomifensine is administered, a sufficient basal dopamine level is reached to allow comparison of dopamine release from drugs of abuse in different areas of the brain without the results being skewed by re-uptake speed variation.